Introducing CAR-T Therapy in Kazakhstan: Establishing Academic-Scale Lentiviral Vector and CAR-T Cell Production

Area of Science:

• Immunotherapy
• Cell and Gene Therapy
• Oncology

Background:

• CAR-T cell therapy is a promising cancer treatment but faces implementation challenges in developing countries.
• Kazakhstan lacked prior experience in advanced cell and gene therapies, highlighting a critical gap in access to immunotherapies.

Purpose of the Study:

• To establish clinical-scale CAR-T production in Kazakhstan, a resource-limited setting.
• To develop and validate a decentralized manufacturing framework for CAR-T therapy.

Main Methods:

• Implemented a complete CAR-T manufacturing pipeline, including in-house lentiviral vector production.
• Utilized automated CAR-T cell processing with the CliniMACS Prodigy system.
• Produced two anti-CD19 CAR lentiviral vectors, one mimicking Kymriah (4-1BB) and another Yescarta (CD28).

Main Results:

• Achieved functional lentiviral vector titers of 1.5 × 10¹⁰ TU/mL.
• Manufactured twelve clinical-scale CAR-T products with a memory-skewed T-cell phenotype.
• CD28-based CAR-T cells showed significantly higher Th1 cytokine production (IFN-γ, TNF-α, IL-2) compared to 4-1BB-based cells, with comparable cytotoxicity.

Conclusions:

• Demonstrated the feasibility of establishing CAR-T production in resource-limited settings.
• Provided a scalable model for CAR-T therapy production suitable for clinical implementation in developing regions.
• Addressed critical gaps in access to advanced immunotherapies in the Central Eurasia region.